Endocrines

Phosphorus is essential for all living organisms. It plays an important role in maintaining biological functions, such as energy metabolism, cell membrane formation, and bone mineralization. Various factors in the intestine, kidneys, and bones regulate the homeostasis of the inorganic phosphate (Pi) concentration in the body. X-linked hypophosphatemia (XLH), the most common form of hereditary hypophosphatemic rickets, is characterized by an impaired mineralization of the bone matrix, hypertrophic chondrocytes with hypophosphatemia, and active vitamin D resistance in childhood. Phosphate-regulating gene with homologies to endopeptidases on the X chromosome was recognized as the responsible gene for XLH. XLH is classified as fibroblast growth factor 23 (FGF23)-related hypophosphatemic rickets. The enhanced FGF23 stimulates renal phosphate wasting by downregulating sodium-dependent Pi cotransporters, NaPi2a and NaPi2c proteins, in the proximal tubules. Recently, transmembrane protein (Tmem) 174 has been identified as a novel regulator of phosphate transporters. This review introduces the role of Tmem174 in the Pi homeostasis in the body. Full article

The association between type 1 diabetes (T1D) and coeliac disease (CD) is well known. Metabolic control of thirty-seven patients aged between 1 and 18 years, with coexisting T1D and CD were evaluated. The control group includes 37 patients affected only by diabetes. All data relating to the metabolic control of all patients were acquired through examination of medical records and CMG reports available on dedicated online platforms. Glucose variability was expressed as Coefficient of Variation (CV) and Standard Deviation of blood glucose values (SD). The formula used for CV computation is: CV (%) = 100 × SD (daily glycemia)/Mean (daily glycemia). Patients with T1D and CD showed a significant reduction in rapid pre-prandial insulin. The same reduction was present if we consider only patients using CGM. In patients without CGM, there was no difference in the doses of basal, pre-prandial and total insulin. Indicators of metabolic control were overlapping between the two groups in patients who used CGM. On the contrary, diabetic and coeliac patients without CGM had increased levels of glycaemic variability indicators and HbA1c. Finally, the percentage of target glycaemic values and >250 mg/dL glycaemic values were significantly decreased and increased, respectively in T1D and CD patients without CGM. With this study we wanted to demonstrate if CGM could improve metabolic control of patients with coexisting T1D and CD. Our data show a worse metabolic control in patients with T1D and CD who did not use CGM. Instead, patients who use CGM, regardless of the concomitant CD, manage to achieve the same glycaemic targets through an adjustment of titration of pre-prandial insulin doses. Full article

Leydig cells, located in the testis interstitial space, are the primary source of testosterone in males. Testosterone plays critical roles in both reproductive and metabolic functions and therefore is essential for male health. Steroidogenesis must be properly regulated since dysregulated hormone production can lead to infertility and metabolic disorders. Leydig cell steroidogenesis relies on the coordinated interaction of various factors, such as hormones and signaling molecules. While luteinizing hormone (LH) is the main regulator of Leydig cell steroidogenesis, other molecules, including growth hormones (GH), prolactin, growth factors (insulin, IGF, FGF, EGF), and osteocalcin, have also been implicated in the stimulation of steroidogenesis. This review provides a comprehensive summary of the mechanisms and signaling pathways employed by LH and other molecules in the stimulation of Leydig cell steroidogenesis, providing valuable insights into the complex regulation of male reproductive and metabolic health. Full article

Background: The prevalence of thyroid disease has seen a rapid increase in recent times, primarily attributed to the fast pace of lifestyles that often result in poor dietary choices, work-life imbalances, social stress, genetic mutations, and improved diagnostic capabilities. However, the precise contribution of these factors to thyroid disease remains a subject of controversy. Consequently, there is a pressing need to gain a comprehensive understanding of the related associations in order to potentially mitigate the associated morbidity and mortality rates. Methods: This study employed association rule mining techniques to reveal hidden correlations among complex and diverse epidemiological connections pertaining to thyroid disease associations. We proposed a framework which incorporates text mining and association rule mining algorithms with exceptionality measurement to simultaneously identify common and exception risk factors correlated with the disease through real-life digital health records. Two distinctive datasets were analyzed through two algorithms, and mutual factors were retained for interpretation. Results: The results confirmed that age, gender, and history of thyroid disease are risk factors positively related to subsequent thyroid cancer. Furthermore, it was observed that the absence of underlying chronic disease conditions, such as diabetes, hypertension, or obesity, are associated with reduced likelihood of being diagnosed with thyroid cancer. Conclusions: Collectively, the proposed framework demonstrates its sound feasibility and should be further recommended for different disease in-depth knowledge discovery. Full article

Interstitial expansion is associated with glomerular filtration rate (GFR) loss in many renal diseases, including diabetic nephropathy. The Renin–Angiotensin System Study (RASS) tested whether a 5-year renin–angiotensin system (RAS) blockade with enalapril or losartan versus placebo slowed progression of early diabetic nephropathy lesions in 285 normoalbuminuric, normotensive, normal/high GFR patients with type 1 diabetes. RASS found no benefit to the RAS blockade on diabetic glomerular lesions but observed an unexpected 50% increase in the fractional volume of the renal cortex which is the interstitium. The effects of the RAS blockade on individual interstitial components––striated collagen, interstitial cells, and peritubular capillaries––were not assessed. We evaluated by electron microscopy changes in fractional volume of each component in seven patients from each group between baseline and five years. At baseline, 49% of the interstitium was collagen, 12% cells, 26% peritubular capillaries, 7% space, and 2% artifact. There was no overall change in the interstitial composition during the RASS. There were no statistically significant effects of treatment group on any interstitial components. Renal volume remained stable in all groups. The RAS blockade affected neither the approximately 50% increase in interstitium fractional volume per cortex nor the parallel increase in all interstitial components that occurred over the five years of the RASS. Full article

Primary amenorrhea (PA) describes the complete absence of menses by the age of 15 years. It is a devastating diagnosis that can affect the adolescent’s view of her femininity, sexuality, fertility and self-image. A normal menstrual cycle can occur only in the presence of: a properly functioning hypothalamus–pituitary axis, well-developed and active ovaries, outflow tract without abnormalities. Any dysfunction in any of these players can result in amenorrhea. PA evaluation includes the patient’s medical history, physical examination, pelvic ultrasonography and initial hormone evaluation, limited to the serum-follicle-stimulating hormone (FSH) and luteinizing hormone, testosterone and prolactin. A karyotype should be obtained in all adolescents with high FSH serum levels. The main causes of PA, whether or not accompanied by secondary sexual characteristics, include endocrine defects of the hypothalamus–pituitary–ovarian axis, genetic defects of the ovary, metabolic diseases, autoimmune diseases, infections, iatrogenic causes (radiotherapy, chemotherapy), environmental factors and Müllerian tract defects. PA management depends on the underlying causes. Estrogen replacement therapy at puberty has mainly been based on personal experience. PA can be due to endocrine, genetic, metabolic, anatomical and environmental disorders that may have severe implications on reproductive health later in life. In some complex cases, a multidisciplinary team best manages the adolescent, including a pediatrician endocrinologist, gynecologist, geneticist, surgeon, radiologist, and psychologist. Full article

The prevalence of diabetes is rising globally; currently, 537 million people worldwide and 37.3 million people in the US are affected. Patients with diabetes have a four-times-greater risk of hospitalization with longer hospital stays and a greater chance of readmission compared to patients without diabetes. Spending on diabetes care as a proportion of global GDP is also projected to increase from 1.8% in 2015 to 2.2% in 2030. The largest component of this medical expenditure is inpatient care in hospitalized patients, accounting for USD 69.7 billion of the total medical cost. Hospitalized patients can develop hyperglycemia without a history of pre-existing diabetes. It has been shown that hyperglycemia in patients without a history of diabetes is also associated with poor hospital outcome. In this review, we discuss the adverse effects of hyperglycemia and hypoglycemia on hospital outcomes; we review recent glycemic targets, recent guidelines’ recommendations, and landmark trials with a brief review on discharge planning, updates on hyperglycemic emergencies, and the use of newer technologies in hospitalized patients such as continuous glucose monitoring devices. Full article

The purpose of this systematic review is to synthesize available studies on sleep health characteristics in adults of African descent with or at risk for cardiometabolic conditions. PubMed, PsycINFO, CINAHL, and Web of Science were searched for original research studies on subgroups of African descent with at least one cardiometabolic risk factor. Studies published in English with measured sleep characteristics were included. Studies focused on participants with severe psychiatric illness, night shift workers, or with a pharmacologic sleep treatment focus were excluded. The risk for bias was assessed using the NHLBI 2021 Quality Assessment Tool. Two reviewers independently synthesized the results before reaching a consensus. Out of 340 studies screened, 35 studies were included. There were 631,756 participants with an average age of 44.3 combined (SD = 16.5) (53% female and 22% Black). Disparities in sleep health characteristics and cardiometabolic health among African American adults were found. Markers of poor cardiometabolic health were associated with disordered sleep. While the studies in this review captured key factors, the study measurement methods were inconsistent, and African Caribbean Americans were underrepresented. The studies demonstrated the intersectionality of poor sleep characteristics, cardiometabolic risk factors, and racial/ethnic groupings. Clinicians should consider these findings when providing care. Full article

Impaired glucagon secretion is a major component of glucose intolerance in type 2 diabetes mellitus (T2D). Glucagon secretion exhibits heterogenous patterns in individuals and across glucose tolerance diagnoses. Characterization of the range of glucagon secretion patterns can help clinicians personalize diabetes care based on glucagon characteristics in addition to glucose and insulin profiles. A total of 102 subjects with normal glucose tolerance, impaired glucose tolerance, and T2D had their glucagon profiles recorded in response to an oral glucose tolerance test. Shapelet analysis was used to identify the most descriptive patterns of early glucagon secretion, and spectral biclustering was employed to identify biclusters of associated subjects and shapelets. The dynamics of glucose, insulin, and glucagon secretion in each cluster were evaluated to identify overall patterns, and the characteristics of the subjects in each cluster were compared. Three clusters were chosen to represent the glucagon patterns. Membership in these three clusters was interpreted based on the presence or lack of extrema in the first 30 min after oral carbohydrate intake. Cluster 1 (n = 23) had a minimum at 30 min and only negative trends. Cluster 2 had a minimum at 10 min and a maximum at 20 min (n = 25). Cluster 3 (n = 40) had a maximum at 10 min and a minimum at 20 min. Subjects in cluster 1 had the lowest average fasting plasma glucose (90.17 mg/dL) and average age (41.39 years) and the highest HOMA-beta score (87.5%), while subjects in cluster 2 had the highest average fasting plasma glucose (102.56 mg/dL) and average age (53.16 years) and the lowest HOMA-beta score (55.77%). Characterization of glucagon dynamics, in addition to glucose and insulin, can aid in personalized treatment approaches and provide greater insight about the underlying dysfunction in glucose regulation. Full article

The communication between brain and peripheral tissues is mediated by neuropeptides that coordinate the functions of each organ with the activities of the entire body in specific environmental conditions. Hypothalamic neuropeptides act as neurotransmitters and hormones to regulate the physiology of food intake, digestion, and metabolism, having a direct or indirect impact on the liver. Investigations on liver pathologies found that dysfunctions of neuropeptides and their receptors are associated with liver disorders such as non-alcoholic fatty liver disease, steatohepatitis, cholestasis, cirrhosis, and liver cancer. In this article, we reviewed neuropeptides that regulate energy homeostasis and lipid and glucose metabolism in the liver and are associated with liver injuries. Firstly, peptides involved in regulatory processes in the brain and liver, such as neuropeptide Y, agouti-related protein, and the galanin family, are related to obesity and its comorbidities, including type 2 diabetes and metabolic syndrome, are presented. Secondly, a comprehensive review of neuropeptides such as secretin, vasoactive intestinal peptide, substance P, and somatostatin, which are involved in liver injuries unrelated to obesity; i.e., cholestasis-induced biliary hyperplasia, cirrhosis, hepatocellular carcinoma, and cholangiocarcinoma, is also presented. The cellular and molecular mechanisms underlining liver injuries related to the dysfunction of these neuropeptides and receptors are also described. Full article

The etiological diagnosis of diabetes conveys many practical consequences for the care of patients, and often of their families. However, a wide heterogeneity in the phenotypes of all diabetes subtypes, including Type 1 diabetes, Type 2 diabetes, and monogenic diabetes, has been reported and contributes to frequent misdiagnoses. The recently revised WHO classification of diabetes mellitus includes two new classes, namely “hybrid forms” and “unclassified diabetes”, which also reflect the difficulties of this etiological diagnosis. During the last years, many studies aiming at identifying homogenous subgroups on refined phenotypes have been reported. Ultimately, such subtyping may improve the diagnosis, prognosis, and treatment of patients on a pathophysiological basis. Here, we discuss the concepts of typical vs. atypical diabetes in the context of autoimmune Type 1 diabetes, Type 2 diabetes, and its monogenic forms. We discuss the contributions of clinical markers, biological tests, particularly islet cell auto-antibodies, and genetics to improving accurate diagnoses. These data support a systematic evaluation of all newly diagnosed diabetes cases. Full article

Background: Obesity constitutes a chronic, low-grade inflammatory status that predisposes people to the development of insulin resistance and cardiometabolic complications. Hypoxia, a main pathological feature of visceral fat in obese individuals, has been shown to affect the secretome of murine 3T3-L1 adipose cells, causing the upregulation of prothymosin-alpha (ProT-α), which is a protein with immunomodulatory functions that was originally found in the thymus. The aim of this case–control observational study was to measure the circulating levels of ProT-α in obese and lean individuals and determine whether such levels are correlated with inflammatory and metabolic parameters. Methods: Sixty-one obese patients (BMI ≥ 30 Kg/m²) and fifty-one age-matched, lean controls (BMI 18.5–24.9 Kg/m²) were recruited in the Endocrinology Unit (“Mater-Domini”) of the University Hospital of Catanzaro, Italy. The exclusion criteria included affliction with acute and systemic inflammatory states (i.e., leukocytosis), recent infectious diseases or vaccinations, obesity complications (i.e., type 2 diabetes mellitus and cardiovascular diseases), hepatic or renal failure, pregnancy and lactation, cancer, use of drugs or alcohol, and smoking. Apart from routine biochemical determinations, serum samples were screened for the presence of ProT-α using an ELISA method and for the presence of a panel of inflammatory cytokines and growth factors via a multiparametric chemiluminescence micro-array. Results: Between the age-matched groups, no statistically significant differences were shown in relation to fasting glucose, HbA1c, liver function tests, lipid profiles, circulating interleukins (IL)-1α, -1β, -2, -4, -8, and -10, MCP-1, TNF-α, VEGF and EGF. Instead, significantly higher median levels were observed in obese patients vs. lean controls with respect to fasting insulin levels (p < 0.001), a classic insulin resistance marker, and IL-6 (p = 0.004). In addition, ProT-α levels were significantly and considerably higher in obese patients compared to lean controls (median ProT-α, 600.0 vs. 411.5 pg/mL, p = 0.004) and showed a moderate to strong positive relationship with fasting insulin levels and selected cytokines (i.e., TNF-α and IL-8). Conclusions: An increase in circulating levels of ProT-α is linked with obesity and can be detected before any clinical cardiometabolic complications develop. ProT-α may represent a novel and sensitive biomarker for inflammation and insulin resistance in obese individuals. Full article

The androgen receptor (AR) is expressed in many cell types, and its related signaling is widely investigated in hormone-dependent cancers such as prostate and breast. The significance of the AR, however, has been detected even in other cancers, including gastric, bladder, kidney, lung, hepatic, and pancreatic, in which growth and spreading are not strictly or notoriously dependent on sex steroid hormone action. The incidence and mortality of these cancers are, however, somewhat related to gender and, specifically, are higher in men than in women, with the ratio reaching 3–4:1 for bladder cancer. This direct correlation between cancer incidence, mortality, and gender makes sex one of the most important risk factors for these cancers and has incited investigation about the role of sex steroid receptors and their activating hormones in gender-related cancers. In these cancers, the AR is often expressed and seems to play a pivotal role in different processes contributing to cancer onset and progression such as growth, spreading, and epithelial to mesenchymal transition (EMT). This manuscript will offer an overview of the role of the AR in many cancers of the respiratory and gastrointestinal systems wherein its role has been at least partially analyzed. Understanding the role of the AR in these tumors could help us to identify a new biomarker for early diagnostic guidance and to develop better therapeutic approaches by directly targeting the AR or its downstream signaling in individual cells of hormone-related cancers at different stages. Full article

Diet has an impact on male reproductive potential, but few studies have focused on the specific impact of food groups or dietary patterns on fertility. Male reproductive health, as indicated by improved semen parameters and increased chances of conceiving, is associated with the Mediterranean diet, while the Western diet is considered a risk factor for male infertility. The potential mechanisms that may explain the impact of these diets on semen quality are still largely unknown. However, numerous studies suggest that nutritional interventions are crucial for the preservation and improvement of male fertility. This review aims to summarize the most recent evidence on the influence of components of the Mediterranean diet on sperm parameters. Unlike other risk factors, dietary modulation represents a great opportunity for improving overall health and can also be an important tool in recommendations for male reproductive health. Full article

Through several pathological mechanisms, chronic stress contributes to the development of “osteosarcopenic obesity”, a clinical syndrome that includes impairments in the structure and function of a patient’s bones, skeletal muscles, and adipose tissue. This syndrome, which could be alternatively called “chronic stress and inflammation syndrome”, has its genesis in early life and, by the age of 50–60 years, affects up to two-thirds of Western populations. Chronic psycho-socioeconomic stress and lifestyle factors, such as a sedentary life, poor quality nutrition, irregular daily schedules, and inadequate sleep, which all act on a genetic and epigenetic predisposition background, play essential pathogenic roles in the development of this widespread syndrome. Key pathogenic mediators are those of the stress system and inflammatory reaction. Lifestyle changes, in combination with stress management, can prevent, arrest, or reverse this debilitating syndrome. Full article

The increased frequency of type 2 diabetes worldwide has led to a concomitant increase in pregnancies complicated by type 2 diabetes for the past 20 years. This is mainly due to two factors: the earlier age of diabetes onset and the advanced age of pregnancy occurrence. Patients with type 2 diabetes in pregnancy show a high frequency of maternal and fetal complications, posing a series of problems in the follow-up of these women. In this narrative review, changes in epidemiology, maternal and fetal complications, and evidence of critical unmet needs before and during pregnancy complicated by type 2 diabetes are reported and discussed to review the possible approaches. Full article

Prostate cancer represents the most common type of cancer among males and the second leading cause of cancer death in men in Western society. In most cases (~70%), PC has a slow and symptom-free growth, whereas it is more aggressive in the remaining patients. Current PC therapies prevalently target the proliferative function of the androgen receptor and may only be effective within short periods, beyond which the disease will progress to metastatic and castration-resistant phenotype. Preclinical and clinical studies are aimed at investigating the molecular basis for prostate cancer spreading. Although considerable efforts have been made to dissect the programs that foster prostate cancer spreading, few biomarkers predictive of metastatic phenotype have yet been identified and few therapeutic options are available for treatment of the metastatic disease. In the present paper, we will discuss innovative aspects of prostate cancer biology, which impinge on the role of cancer-associated fibroblasts and the released matrix metalloproteinases in the disease progression. Investigating these aspects might allow the discovery of clinically actionable biomarkers to target in the advanced stages of prostate cancer. Full article

Type-2 diabetes mellitus (T2D) is one of the leading non-communicable diseases of global concern. Knowing the exact mechanism of action of available antidiabetic agents, particularly natural products, may assist in providing effective therapeutic solutions. The antidiabetic action of Helianthus annuus (sunflower) seed has been established; however, the molecular mechanism of action, especially the essential oil, is lacking. The study explored network pharmacology and molecular docking studies to determine the active phytoconstituents, signaling pathways, and probable therapeutic targets to determine the antidiabetic potential of sunflower seed essential oil. Preliminary analysis established 23 target genes with 15 phytoconstituents involved in T2D which all passed Lipinski’s rule of five with no violation. Three pathways were proposed by KEGG analysis as therapeutic targets for T2D development with PPAR as the major route affecting PPARA, FABP4, PPARD, PPARG, and CPT2 genes. Molecular docking investigation confirmed the effectiveness of active SSEO compounds against the identified genes (targets) and established phylloquinone, linoleic acid, tricosylic acid, and lignoceric acid as the probable drug candidates that could offer laudable therapeutic effects in an effort towards T2D management. Thereby, we present an insight toward understanding the mechanism of the antidiabetic action of sunflower seeds via the stimulation of glucose to enhance insulin release. Full article

Background: The differential responses of the myokine irisin, in combination with changes in markers and regulators of bone remodeling to high-intensity interval exercise of high and low impact, were examined in 18 young adult females (22.5 ± 2.7 years). Methods: Participants performed two high-intensity interval exercise trials in random order: running on a treadmill and cycling on a cycle ergometer. Trials consisted of eight 1 min running or cycling intervals at ≥ 90% of maximal heart rate, separated by 1 min passive recovery intervals. Blood samples were collected at rest (pre-exercise) and 5 min, 1 h, and 24 h following each exercise trial. Irisin, osteocalcin, sclerostin, osteoprotegerin (OPG), receptor activator nuclear factor kappa-β ligand (RANKL), and parathyroid hormone (PTH) were analyzed in serum, with post-exercise concentrations being corrected for exercise-induced changes in plasma volume. Results: Irisin was elevated 24 h post-exercise compared to its resting values in both trials (20%, p < 0.05) and was higher after cycling compared to running (exercise mode effect, p < 0.05) with no interaction. Osteocalcin, sclerostin, PTH, and RANKL increased from pre- to 5 min post-exercise (18%, 37%, 83%, and 33%, respectively, p < 0.05), returning to baseline levels in 1 h, with no trial or interaction effects. OPG showed a time effect (p < 0.05), reflecting an overall increase at 5 min and 1 h post-exercise, which was not significant after the Bonferroni adjustment. Conclusions: In young adult females, high-intensity interval exercise induced an immediate response in markers and regulators of bone remodeling and a later response in irisin concentrations, which was independent of the gravitational impact. Full article